The overall objective of this exploratory/development proposal (R21) is to invent a novel technology to produce elastomeric microelectrode arrays capable of simultaneous mechanical stimulation and recording of electrophysiology from living brain tissue in vitro. Because the stretchable microelectrode arrays (SMEAs) are an integral component of the culture substrate, they will enable the long-term study of neuronal function pre-, during, and post-mechanical stimulation. If we are successful, SMEAs will make possible fundamental new studies in the fields of in vitro electrophysiology, mechano-biology, and traumatic brain injury research, to complement in vivo studies. We are significantly encouraged by our recent discovery that nanometer thick metallic conductors patterned on silicone rubber remain conductive after stretch cycles >20%. To obtain fully functional SMEAs, we must overcome multiple hurdles of biological and electrotechnical nature: in-situ recording of electrophysiology during mechanical injury remains a significant challenge and the fabrication of electronic circuits on elastomeric surfaces is still novel. We plan to first build a functional 2X2 SMEA to further develop thin-film patterning and encapsulation technologies on elastomeric membranes, and to use this 2X2 array as a test bed to record electrophysiology from organotypic hippocampal slice cultures. The robustness of the system to severe mechanical deformations consistent with head injury will be evaluated. Concurrently, the fabrication technology will be advanced to produce 4X4 SMEAs rivaling the feature size and density of existing rigid MEAs. This proposal is relevant to public health because it will provide a new tool to study traumatic brain injury in ways not possible today. The potential benefit to public health of our invention is significant given the societal cost of TBI annually: 60,000 deaths and 85,000 injured persons with long-term disabilities. If we are successful, our SMEAs technology will have a major impact on the study of injury-induced neuronal dysfunction and the investigation of central nervous system repair strategies to restore lost function. Added benefits include reduced cost, higher throughput for screening compounds, and reduced animal use compared to in vivo models of TBI. [unreadable] [unreadable] [unreadable]